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Molecules (Basel, Switzerland) May 2021Enzymes are highly specific biological catalysts that accelerate the rate of chemical reactions within the cell. Our knowledge of how enzymes work remains incomplete.... (Review)
Review
Enzymes are highly specific biological catalysts that accelerate the rate of chemical reactions within the cell. Our knowledge of how enzymes work remains incomplete. Computational methodologies such as molecular mechanics (MM) and quantum mechanical (QM) methods play an important role in elucidating the detailed mechanisms of enzymatic reactions where experimental research measurements are not possible. Theories invoked by a variety of scientists indicate that enzymes work as structural scaffolds that serve to bring together and orient the reactants so that the reaction can proceed with minimum energy. Enzyme models can be utilized for mimicking enzyme catalysis and the development of novel prodrugs. Prodrugs are used to enhance the pharmacokinetics of drugs; classical prodrug approaches focus on alternating the physicochemical properties, while chemical modern approaches are based on the knowledge gained from the chemistry of enzyme models and correlations between experimental and calculated rate values of intramolecular processes (enzyme models). A large number of prodrugs have been designed and developed to improve the effectiveness and pharmacokinetics of commonly used drugs, such as anti-Parkinson (dopamine), antiviral (acyclovir), antimalarial (atovaquone), anticancer (azanucleosides), antifibrinolytic (tranexamic acid), antihyperlipidemia (statins), vasoconstrictors (phenylephrine), antihypertension (atenolol), antibacterial agents (amoxicillin, cephalexin, and cefuroxime axetil), paracetamol, and guaifenesin. This article describes the works done on enzyme models and the computational methods used to understand enzyme catalysis and to help in the development of efficient prodrugs.
Topics: Acyclovir; Atenolol; Atovaquone; Catalysis; Chemistry, Pharmaceutical; Decitabine; Dopamine; Enzymes; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Molecular Conformation; Nucleosides; Phenylephrine; Prodrugs; Protons; Quantum Theory; Software; Technology, Pharmaceutical; Temperature; Tranexamic Acid
PubMed: 34071328
DOI: 10.3390/molecules26113248 -
Current Opinion in Pediatrics Aug 2015Since 2008, beta-blockers have become first-line treatment for infantile hemangiomas, the most common tumor of infancy. Their role is also being explored in the... (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
Since 2008, beta-blockers have become first-line treatment for infantile hemangiomas, the most common tumor of infancy. Their role is also being explored in the treatment of other childhood vascular tumors.
RECENT FINDINGS
Recent research has demonstrated that propranolol is a more effective and safer treatment for infantile hemangiomas than previous therapeutic options. It is most effective when initiated during the tumor's proliferative phase. Other oral beta-blockers such as atenolol and nadolol are less studied, but may offer similar efficacy. Topical beta-blockers such as timolol appear to be effective in treating small, superficial infantile hemangiomas. Beta-blockers have shown variable results for the treatment of other vascular tumors of childhood, such as pyogenic granulomas, kaposiform hemangioendotheliomas, and tufted angiomas.
SUMMARY
Propranolol has revolutionized the treatment of infantile hemangiomas, and other beta-blockers provide promising alternatives. Unanswered questions remain about the optimal choice of agent, delivery mechanism, dosage, need for pretreatment evaluation or ongoing monitoring, and duration of therapy. The role of beta-blockers in treating other types of vascular tumors requires further study.
Topics: Administration, Oral; Administration, Topical; Adrenergic beta-Antagonists; Atenolol; Child, Preschool; Facial Neoplasms; Humans; Infant; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Propranolol; Skin Neoplasms; Timolol; Treatment Outcome; Vascular Neoplasms
PubMed: 26087423
DOI: 10.1097/MOP.0000000000000238 -
Advanced Emergency Nursing Journal 2017Approximately 40% of all women report experiencing headaches during the postpartum period, regardless of a previous headache history. This case narrative describes the...
Approximately 40% of all women report experiencing headaches during the postpartum period, regardless of a previous headache history. This case narrative describes the clinical case of a 22-year-old woman who presented for the evaluation of an intractable headache for 2½ weeks. It demonstrates the inherent difficulty in diagnosing patients not presenting with "textbook" symptoms and highlights the fact that signs and symptoms of eclampsia/preeclampsia, such as elevated blood pressure, may fall below the threshold for hypertensive emergencies and not be considered in the differential. Emergency department providers must possess a strong knowledge base and skill set to recognize subtle presentations and direct care accordingly to ensure positive patient outcomes.
Topics: Analgesics; Antihypertensive Agents; Atenolol; Diagnosis, Differential; Drug Therapy, Combination; Female; Headache; Humans; Magnesium Sulfate; Pain Management; Pain Measurement; Postpartum Period; Pre-Eclampsia; Pregnancy; Young Adult
PubMed: 29095177
DOI: 10.1097/TME.0000000000000162 -
Dermatology Online Journal Jul 2015Infantile hemangiomas (IH) are common childhood vascular tumors. Treatment of IH has undergone rapid change in recent years. Since 2008, oral propranolol has been... (Review)
Review
Infantile hemangiomas (IH) are common childhood vascular tumors. Treatment of IH has undergone rapid change in recent years. Since 2008, oral propranolol has been used to treat complicated IH and has proven superior to previously used therapies. More recently, the efficacy of other systemic beta blockers, specifically atenolol and nadolol, has been reported. In addition, topical timolol solution has been effective for treatment of smaller, more superficial IH. The purpose of this article is to review the current literature of beta-blocker therapy for IH.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Atenolol; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Hemangioma, Capillary; Humans; Infant; Male; Nadolol; Propranolol; Skin Neoplasms; Timolol; Treatment Outcome
PubMed: 26436966
DOI: No ID Found -
Environmental Toxicology and... Sep 2023Blood pressure medications like atenolol are detected in aquatic ecosystems. The objectives here were to (1) map the global presence of atenolol in surface water and... (Review)
Review
Blood pressure medications like atenolol are detected in aquatic ecosystems. The objectives here were to (1) map the global presence of atenolol in surface water and sewage; (2) present current knowledge regarding removal efficiency and degradation of atenolol; (3) identify biological endpoints sensitive to exposure; (4) reveal molecular biomarkers that may be useful for exposure studies in fish; (5) determine whether toxicology studies are within environmental relevance. In fish, atenolol exposure affects endocrine and immune systems, metabolism, and epigenetics. Fewer than half of all studies measuring biological responses use environmentally-relevant concentrations. Heart rate appeared most sensitive to atenolol exposure relative to other endpoints. Data are lacking for behavioral responses to atenolol. Molecular biomarkers for atenolol may include those associated with acute kidney injury, cholestasis, and hypertriglyceridemia. Head kidney and liver may therefore be useful for detecting atenolol-induced effects. This review synthesizes knowledge regarding atenolol-induced toxicity in fish.
Topics: Animals; Atenolol; Ecosystem; Fishes; Biomarkers
PubMed: 37481051
DOI: 10.1016/j.etap.2023.104236 -
Journal of Molecular Modeling Jun 2022The purpose of this work was to investigate, via DFT calculations, the molecularly imprinted polymer (MIP) for atenolol (ATL) β-blocker evaluating distinct functional...
The purpose of this work was to investigate, via DFT calculations, the molecularly imprinted polymer (MIP) for atenolol (ATL) β-blocker evaluating distinct functional monomers (FMs), solvents, and cross-linker agents (CLAs). As the main result, we could determine from structural and thermodynamic data the best MIP synthesis protocol as being: p-vinyl benzoic acid (APV) as FM, toluene as solvent, and pentaerythritol triacrylate (PETRA) as CLA. We believe this rational design can be very useful for experimentalists in an attempt to perform an efficient synthesis of a MIP for this important β-blocker drug.
Topics: Atenolol; Polymers; Solvents; Thermodynamics
PubMed: 35654919
DOI: 10.1007/s00894-022-05171-2 -
Archives de Pediatrie : Organe Officiel... Nov 2015
Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Anti-Obesity Agents; Anticonvulsants; Aorta; Aortic Aneurysm; Atenolol; Cleft Palate; Female; Fructose; Hemangioma; Humans; Losartan; Male; Marfan Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Skin Neoplasms
PubMed: 26385645
DOI: 10.1016/j.arcped.2015.08.001 -
Journal of Hazardous Materials Feb 2023The recalcitrant β-blockers have been widely detected in aquatic environments up to several hundred μg/L, which are major contributors to β1 antagonistic activities...
The recalcitrant β-blockers have been widely detected in aquatic environments up to several hundred μg/L, which are major contributors to β1 antagonistic activities in wastewater. Their biodegradation mechanisms remain obscure, hindering the development of efficient removal techniques. This study constructed the biodegradation pathways for three typical β-blockers, namely atenolol, metoprolol, and propranolol, assessed the toxicity of their major biotransformation products, and identified the key enzyme catalyzing the O-dealkylation reaction leading to pollutant mineralization. Atenolol and metoprolol degradation was more efficient than that of propranolol by activated sludge, producing metoprolol acid (MTPA) as a major intermediate. Hydrogenophaga sp. YM1 isolated from activated sludge possess the α-ketoglutarate dependent dioxygenase (TfdA) responsible for O-dealkylation of MTPA and propranolol, producing 4-hydroxyphenylacetic acid (4-HPA) that can be further degraded and ultimately enters the TCA cycle. The role of TfdA was verified by proteomics, enzyme stimulation/inhibition tests, and gene knockout experiments. Molecular docking suggests its different interactions with MTPA and propranolol. Acetate facilitated the degradation of β-blockers efficiently. The results may shed light on enhanced biological removals of broader β-blockers and their transformation products in the environment.
Topics: Wastewater; Propranolol; Metoprolol; Sewage; Atenolol; Molecular Docking Simulation; Adrenergic beta-Antagonists
PubMed: 36417780
DOI: 10.1016/j.jhazmat.2022.130338 -
The Science of the Total Environment Dec 2023The presence of pharmaceuticals in surface water and wastewater has been an increasing area of research since they can represent a possible route for human exposure when...
The presence of pharmaceuticals in surface water and wastewater has been an increasing area of research since they can represent a possible route for human exposure when these waters are used to irrigate crops. The concentration of these drugs in crops depends on their uptake and translocation within plants. A less recognized question is that over 50 % of pharmaceuticals are chiral compounds, but there is little knowledge about their enantioselectivity in plants. In this study, we evaluated the uptake, bioconcentration, and translocation of enantiomers of atenolol, a commonly used beta-blocker, in Arabidopsis thaliana cells and Lactuca sativa plants under hydroponic conditions. Atenolol was taken up by Arabidopsis thaliana cells during 120 h of exposure to solutions with 1 mg/L of R/S-(±)-atenolol. A moderate preference for R-(+)-atenolol over S-(-)-atenolol was observed, with the enantiomeric fraction (EF) reaching 0.532 ± 0.002 for the R enantiomer. Atenolol was also taken up and translocated by Lactuca sativa after hydroponic cultivation in nutrient solutions containing 1 or 10 μg/L R/S-(±)-atenolol. Moderate enantioselectivity was detected in the treatment with 10 μg/L, and the EF after 168 h was 0.42 ± 0.01, suggesting that S-(-)-atenolol was preferentially accumulated. Selectivity was also observed in the translocation factor (TF), calculated as the ratio of the concentration in the leaves over that in the roots. As many emerging contaminants are chiral, our findings highlight the importance to consider their fate and risks in terrestrial ecosystems at the enantiomer scale.
Topics: Humans; Atenolol; Arabidopsis; Stereoisomerism; Ecosystem; Embryophyta; Crops, Agricultural; Pharmaceutical Preparations
PubMed: 37657535
DOI: 10.1016/j.scitotenv.2023.166720 -
Spectrochimica Acta. Part A, Molecular... Jan 2024Fixed-dose combinations for treatment of hypertension are observed in many dosages in the global market because of their high efficacy compared to single component...
Fixed-dose combinations for treatment of hypertension are observed in many dosages in the global market because of their high efficacy compared to single component dosage forms. One of these effective combinations is atenolol/amlodipine which is usually administered to patients with hypertension. Hence, development of facile, accurate, and sensitive methods for simultaneous estimation of atenolol and amlodipine is of great importance for quality control testing and pharmacokinetic studies. In our study, we developed two spectrofluorimetric methods to estimate both compounds in different pharmaceuticals. The first method is based on the estimation of atenolol and amlodipine by double-scan conventional spectrofluorimetry where the fluorescence intensities of atenolol and amlodipine were measured at 299 and 434 nm after excitation at 274 and 358 nm, respectively. The second method depends on synchronous spectrofluorimetric measurements at Δλ = 70 nm, where atenolol is assayed at 266 nm and amlodipine is assayed at 363 nm. Methods' optimizations were carried out to select the optimum conditions that render high selectivity and sensitivity. Such optimizations included assessment of solvents, surfactants, buffer volumes and pHs. The conventional spectrofluorimetric method was rectilinear over concentration range of 30.0-300.0 ng mL for atenolol and 0.25-7.00 µg mL for amlodipine while the synchronous spectrofluorimetric method showed linearity over the ranges of 0.60-6.00 µg mL for atenolol and 0.25-7.00 µg mL for amlodipine with low detection limits (≤0.12 µg mL) for both compounds in the two methods. It is the first work that demonstrates estimation of atenolol and amlodipine in their combinations by conventional and synchronous spectrofluorimetry. Both methods were applied to estimate atenolol and amlodipine in different pharmaceuticals with high %recovery and low %RSD.
Topics: Humans; Amlodipine; Atenolol; Spectrometry, Fluorescence; Pharmaceutical Preparations
PubMed: 37864972
DOI: 10.1016/j.saa.2023.123532